Cortical and thalamic axon pathfinding defects in Tbr1 , Gbx2 , and Pax6 mutant mice: Evidence that cortical and thalamic axons interact and guide each other
Abstract
During development, cortical areas establish precise reciprocal projections with corresponding thalamic nuclei. Pioneer axons from the cortex and thalamus first meet in the intermediate zone of the subcortical telencephalon (subpallium). Their close interactions in the subpallium suggest that they may use each other for guidance. To test this hypothesis, the development of corticothalamic and thalamocortical connections was studied in mice with mutations of transcription factor genes expressed specifically in the cortex ( Tbr1 ), the dorsal thalamus ( Gbx2 ), or both ( Pax6 ). In Tbr1 mutants, cortical pioneer axons entered the subpallium at the appropriate time, but most stopped growing without entering the diencephalon. Surprisingly, thalamic axons (which do not express Tbr1 ) deviated into the external capsule and amygdala regions, without entering the cortex. Conversely, in most Gbx2 mutants, thalamic axons were reduced in number and grew no farther than the subpallium. Cortical axons (which do not express Gbx2 ) grew into the subpallium but did not enter the diencephalon. In one Gbx2 – /– case, sparse thalamocortical and corticothalamic projections both developed, but in no case did one projection reach its target and not the other. In Pax6 mutants, neither corticothalamic nor thalamocortical axons reached their targets. These results suggest that thalamocortical and corticothalamic projections may not form independently. After reaching the subpallium, each projection may require a molecularly intact reciprocal projection for further guidance. This type of mechanism ensures that thalamocortical and corticothalamic axons project reciprocally. However, the exact nature of the interaction between cortical and thalamic pioneer axons remains to be elucidated. J. Comp. Neurol. 447:8–17, 2002. © 2002 Wiley‐Liss, Inc.
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Tbr1−/− mice have defective cortical morphology, neuronal migration, and axonal projections, which are not detected in Tbr1+/− mice.
“Tbr1−/− mice have defective cortical morphology, neuronal migration, and axonal projections [156, 157], which are not detected in Tbr1+/− mice that model the haploinsufficiency observed in patients more faithfully.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [156]
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- Authors
- Hevner, R. F., Miyashita‐Lin, E., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Rubenstein, John L.R.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2002-04-08
- Volume
- 447
- Issue
- 1
- Pages
- 8-17
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2077423081
- Cited by
- 202
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 9 · 2014: 5 · 2013: 10 · 2012: 12
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2k02mh001046-06, 7k08ns001973-06)
- National Institute of Mental Health (K02 MH01046-01)
- National Institute of Neurological Disorders and Stroke (NS01973, R01NS034661, NS34661-01A1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- corticothalamic projections, thalamocortical connections, axon guidance, Tbr1, Gbx2, Pax6, thalamus, cerebral cortex, subpallium, intermediate zone, pioneer axons, reciprocal projections, transcription factor mutants
- MeSH terms
- PAX6 Transcription Factor, Animals, Animals, Newborn, Carbocyanines, Cell Communication, Cell Differentiation, Cerebral Cortex, DNA-Binding Proteins, Eye Proteins, Female, Fetus, Fluorescent Dyes, Mutation, Nervous System Malformations, Neural Pathways, Repressor Proteins, Thalamus, Mice, Knockout, Homeodomain Proteins, Growth Cones, Internal Capsule, T-Box Domain Proteins, Mice, Paired Box Transcription Factors
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